Angiotensin II Increases the mRNA Expression of Dopamine D2 and D4 Receptors in Rat Mesangial Cell

• Main Authors: Yu-Feng Lin, 林裕峯
• Other Authors: Kwan-Dun Wu
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/55082609142515000148

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 96 === Aim: Diabetes mellitus is the main cause for renal failure. In the early stage of diabetic nephropathy, there are mesangial hypertrophy, glomerular hyperfiltration, and albuminuria. The early changes in mesangial cell are believed to be related to the deterioration of the renal function. Mesangial cell is a kind of smooth muscle cell, a kind of fibroblast, and also a kind of macrophage. There are target sites of vasoactive agents on it, including vasoconstrictors (ex. angiotensin II) and vasodilators (ex. dopamine). By the experimental diabetes rat model, the production of dopamine in the kidney increases, this may activate the dopaminergic system in the kidney, and causes glomerular hyperfiltration. In diabetes rat model it is also said that there is relationship between dopamine D2-like receptors and glomerular function. Dopamine receptor is a kind of G protein-coupled receptors, which may influence the cell proliferation, differentiation, and survival by intra-cellular MAPK pathway. This study was designed to find out: under the high glucose or angiotensin II stimulation as diabetes status, the mesangial cell may change the mRNA expression of dopamine D2-like receptors (either dopamine D2 receptor or dopamine D4 receptor). Methods: This study set up an adequate culturing environment and condition for the primary culture rat mesangial cell. Furthermore, the existence of dopamine D2 and D4 receptors together with MCP-1 mRNA expression in primary culture rat mesangial cell were proved by RT-PCR. Then, the angiotensin II or high glucose was added in the cell culture environment to see the different mRNA expression of dopamine D2 receptor, dopamine D4 receptor, and MCP-1 in separate time points. Finally, the dopamine D2 or D4 agonist and antagonist were added respectively to the culture environment in order to see the changes of MCP-1 mRNA expression in the primary culture rat mesangial cell. Results: After the incubation of cells for 12 hours in 10-6M angiotensin II, the dopamine D2 receptor and dopamine D4 receptor mRNA expression increased. Additionally, the mRNA expression of MCP-1 increased apparently after 8 hours of the effect of angiotensin II. 30nM high glucose in the culture environment also increased the mRNA expression of dopamine D2 receptor, dopamine D4 receptor, and MCP-1, but these should be the effect of osmolarity. No apparent changes of mRNA expression in MCP-1 was found under the effect of dopamine D2 or D4 agonist and antagonist. Conclusions: This study found the mRNA existence of dopamine D2 and D4 receptors in primary culture rat mesangial cell, and this study also established a well-performed cellular phenotype model with adequate culturing environments and conditions. Furthermore, this study demonstrated that angiotensin II increased the mRNA expression of dopamine D2、D4 receptors and MCP-1. Further study is necessary for the underlying mechanism and their relationships to the MAPKs pathway.